Liver microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid.
Arachidonic acid is oxidatively metabolized by rat liver microsomes at a rate of approximately 5 nmol per min per mg of protein at 25 degrees C. This reaction is dependent on the presence of NADPH and oxygen. Studies with various inhibitors indicate a role for membrane-bound cytochrome P-450 in the transformation of arachidonic acid to a mixture of hydroxy acid derivatives. The stoichiometry of the reaction conforms to that of a monooxygenase reaction--i.e., one mole of NADPH is oxidized per mole of oxygen utilized--suggesting a reaction mechanism different from that proposed for lipid peroxidation reactions. No evidence for the formation of prostaglandin-like metabolites was obtained. The diene character of some of the metabolites formed suggests another role for cytochrome P-450--i.e., participation in hydrogen abstraction reactions for the activation of various substrates.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013057:Spectrum Analysis
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D009249:NADP; D003577:Cytochrome P-450 Enzyme System